This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 1. HIV Lipodystrophy Syndrome (HLS) is associated with: a) accelerated whole-body lipid kinetics with an increase in total and net lipolysis. b) absence of a proportional increase in fatty acid oxidation. c) increased intra- adipocyte and intra-hepatic re-esterification. d) increased turnover rate of apoB-100. 2. Leptin therapy in HLS will stimulate fat oxidation and shift fuel selection for energy requirements from carbohydrate to lipid. Free fatty acids released as a result of lipolysis will be shunted away from intra-hepatic re-esterification, and VLDL apoB-100 synthesis towards oxidative disposal, thus improving hypertriglyceridemia.